The long term objective of this project is a better understanding of the role of genetic and environmental factors in human neuropsychiatric disorders through the study of the Gilles de 1a Tourette's syndrome (GTS), obsessive compulsive disorder (OCD) and attention deficit disorder (ADD). Recent research has led to several notable advances in our understanding of GTS, OCD and related conditions: 1) there is a greater range of phenotypic expression for GTS (including some chronic tics, some forms of OCD and possibly some attentional problems); 2) GTS and related disorders are much more common than had previously been thought; and 3) the syndrome appears to be transmitted as an autosomal dominant trait. Furthermore, the prevalence of GTS and associated illnesses and their debilitating effects on those afflicted makes these conditions a major public health problem. Understanding the genetic and epigenetic factors important for the manifestation of GTS and associated behaviors will be of direct benefit to patients concerned about recurrence in their families; ultimately, clarifying the genetics of these conditions may elucidate their pathogenesis. Results from our ongoing analyses suggest that there is an etiologic relationship between GTS, OCD and some types of ADD. In this application, we are proposing to collect additional data that will make it possible to characterize more completely the nature of the relationship between GTS, OCD, attentional difficulties and other traits. We will expand our sample to a total of 100 families of child OCD probands. These families will allow a more direct comparison of families of young children. Since GTS is a childhood disorder, it is important to compare expression of the syndrome to the expression of OCD in children. Studying the families of childhood OCD probands should help to clarify further the transmission of both GTS and OCD and to further our understanding of the familial relationship of the two disorders. In addition, data collection for a family study of GTS and ADD will begin. These data will allow a more complete analysis of the relationship between GTS and ADD. Preliminary results from this study suggest that there may be at least two different types of GTS + ADD individuals: those who have two independent disorders and those in whom the ADD is part of the manifestation of GTS. These family data will allow an examination about the existence of these two types. Finally, we plan to expand a prospective study of young unaffected children who have first degree relatives affected with GTS and/or OCD. Forty-four young children have already been enrolled in the study. We plan to enroll the families of 50 additional children at risk for GTS, 90 children at risk for OCD and 40 control children. This study will help to identify "non-genetic" factors important for onset and variable expressions of GTS and related disorders. Data from these new family and prospective study samples will help identify specific genetic and environmental factors associated with the variable expression of GTS and related behaviors. In all cases, information will be obtained by direct structured assessment of all pertinent family members.